Reproduction Flashcards
Agenesis
Absent organ due to absent primordial tissue
Aplasia
Absent organ despite presence of primordial tissue
Deformation
Extrinsic disruption
Occurs after embryonic period
Hypoplasia
Incomplete organ development
Primordial tissue present
Malformation
Intrinsic disruption
Occurs during embryonic period (3-8 weeks)
Teratogenic Effects of ACEI
Renal damage
Teratogenic Effects of Alkylating Agents
Absence of digits
Multiple abnormalities
Teratogenic Effects of Aminoglycosides
“A mean guy hit the baby in the ear”
CN VIII toxicity
Teratogenic Effects of Carbamazepine
Neural tube defects
Craniofacial defects
Fingernail hypoplasia
Developmental delay
IUGR (IntraUterine Growth Restriction )
Teratogenic Effects of Diethylstilbestrol (DES)
Vaginal clear cell carcinoma
Congenital Mullerian anomalies
Teratogenic Effects of Folate Antagonists
Neural Tube Defects
Teratogenic Effects of Li
Ebstein’s Anomaly (Atrialized RV)
Teratogenic Effects of Phenytoin
Fetal hydantoin syndrome: microcephaly, dysmorphic craniofacial features, hypoplastic nails and distal phalanges, cardiac defects, IUGR (IntraUterine Growth Restriction ), mental retardation
Teratogenic Effects of Tetracyclines
Discolored Teeth
Teratogenic Effects of Valproate
Inhibition of maternal folate absorption –> neural tube defects
Teratogenic Effects of Warfarin
“Do not wage Warfare on the baby, keep in Heppy with Heparin (does not cross the placenta)”
Bone deformities, fetal hemorrhage, abortion, ophthalmologic abnormalities
Teratogenic Effects of Thalidomide
"Limb Defects with tha-LIMB-domide" Limb defects (flipper limbs)
Teratogenic Effects of EtOH
Leading cause of birth defects and mental retardation
Fetal Alcohol Syndrome
Teratogenic Effects of Cocaine
Abnormal fetal development and fetal addiction; Placenta abruption
Teratogenic Effects of Smoking (nicotine, CO)
Preterm labor, Placental problems, IUGR (IntraUterine Growth Restriction ), ADHD
Teratogenic Effects of Iodide (Lack or Excess)
Congenital Goiter or Hypothyroidism (cretinism)
Teratogenic Effects of Maternal Diabetes
Caudal regression syndrome (anal atresia to sirenomelia), Congenital Heart Defects (Transposition of the Great Vessels), Neural Tube Defects
Teratogenic Effects of Excess Vit A
Extremely high risk for spontaneous abortions and birth defects (cleft palate, cardiac abnormalities)
Teratogenic Effects of X Rays
Microcephaly, Mental Retardation
Fetal Alcohol Syndrome
Mental Retardation, Pre and Post Natal Developmental Retardation, Microcephaly, Holoprosencephaly, Facial Abnormalities, Limb Dislocation, Heart and Lung Fistulas
Source of Estrogen
Ovary –> 17β-estradiol
Placenta –> estriol
Adipose tissue –> estrone via aromatization
Potency of different kinds of estrogens
Estradiol > Estrone > Estiol
Estrogen Function
Development
In menstrual cycle
Receptors
Blood
Development of genitalia, breast, and female fat distribution
Growth of follicle, endometrial proliferation, and ↑ myometrial excitability
Feedback inhibition of LH and FSH and then LH surge
Stimulation of prolactin secretion (but blocks it’s action at the breast)
Upregulates estrogen, LH, and progesterone receptors
↑ Transport proteins, SHBG, HDL, ↓LDL
How does pregnancy change estrogen levels
50x ↑ in estradiol and estrone
1000x ↑ in estiol (indicator of fetal well being
Mechanism of estrogen receptor
Expressed in cytoplasm
When bound with ligand, translocates to the nucleus
Molecular cascade in Theca Cells
Pulsatile GnRH –> LH –> Desmolase
D turns cholesterol in to androstenedione
Molecular cascade in Granulosa Cells
Pulsatile GnRH –> FSH –> Aromatase
A turns androstenedione into estrogen
Source of Progesterone
Corpus Luteum, Placenta, Adrenal Cortex, Testes
Elevation of Progesterone indicates…
Ovulation
Function of Progesterone
Menstural cycle
Receptors
Pregnancy
Stimulation of endometrial glandular secretions and spiral artery development
Maintains endometrium to support implantation
–/ LH and FSH
↓ myometrial excitability
↓ estrogen receptor expressivity
Maintain pregnancy
Production of thick cervical mucus (inhibits sperm entry into uterus)
↑ Body Temp
Uterine smooth muscle relaxation (prevents contractions)
Tanner Stages of Sexual Development
I: Childhood
II: Pubic hair appears (Pubarche), Breast bud forms (Thelarche)
III: Pubic hair darkens and becomes curly. Penis size/length and breasts enlarge
IV: Penis width ↑, Darker scrotal skin, Development of glans, raised areolae
V: Adult. Areolae are no longer raised
Follicular Phase
Estrogen
FSH
LH
Progesterone
Estrogen: Stead rise
FSH: Rises slightly then decreases slightly
LH: Rises slightly then decreases slightly
Progesterone: Low
Luteal Phase
Estrogen
FSH
LH
Progesterone
Estrogen: decreases, then spikes briefly before decreasing again
FSH low
LH low
Progesterone: increases then decreases
Ovulation
Estrogen
FSH
LH
Progesterone
GnRH
Temp
Estrogen: just past peak
FSH: low surge
LH: high surge
Progesterone: beginning to rise
↑ in GnRH receptors on ant pituitary
↑ Temp (due to progesterone)
Basic schematic of menstrual cycle
↑ estrogen –> LH surge –> Ovulation –> Progesterone (from corpus luteum) –> Progesterone levels fall –> menstruation (apoptosis of endometrial cells)
Length of Follicular phase
Variable
Length of Luteal phase
Constant 14 days
When is follicular growth fastest?
2nd week of proliferative phase (follicular phase)
Oligomenorrhea
Cycle > 35 days
Polymenorrhea
Cycle < 21 days
Menometrorrhagia
Heavy, irregular menstruation at irregular intervals
Mittelschmerz
Blood from ruptured follicle or follicular enlargement causes peritoneal irritation that can mimic appendicitis
Primary Oocytes
N
C
When do they enter and complete meiosis I
2N 4C
Begin meiosis I during fetal life and complete meiosis I just prior to ovulation
When is meiosis II arrested?
Until when?
“Arrested until egg MET sperm”
Meiosis II arrested at Metaphase II until fertilization
If fertilization does not occur within 1 day what happens to secondary oocytes?
Degenerate
Oogenesis
Names of cells with N and C
Oogonium (2N 2C) –> Primary Oocyte (2N 4C) –> Secondary Oocyte (1N 2C) –> Ovum (1N 1C)
Where and When does fertilization most commonly occur?
Upper end of fallopian tube (ampulla) within 1 day of ovulation
When does implantation within the wall of the uterus occur?
Within 6 days after fertilization
What secretes hCG?
When is hCG first detectable in blood and urine?
Trophoblast secretes hCG
Detectable in blood 1 week after conception
Detectable in urine 2 weeks after conception
Lactation
When does it occur?
What has changed chemically that allows it to happen?
What is required to maintain lactation?
Occurs after labor because progesterone ↓ and this allows lactation to occur
Suckling is required to maintain lactation: ↑ nerve stimulation –> ↑ oxytocin and prolactin
Prolactin
What does it do?
Induces and maintains lactation and ↓ reproductive function
Oxytocin
What does it do?
Helps with milk letdown and involved with uterine contraction
hCG
Source
Function
Uses
Syncytiotrophoblast of placenta
Maintains corpus luteum (and thus progesterone) for 1st trimester by acting like LH
Used to detect pregnancy
Why is hCG not needed in 2nd and 3rd trimesters?
Placenta synthesizes its own estriol and progesterone
Elevated hCG in pathological states
Hydatidiform moles, choriocarcinoma
Average age of menopause?
What makes it earlier?
Average age at onset is 51
Earlier in smokers
What is happening hormonally in menopause?
↓ estrogen production becuse of ↓ # of follicles
↑↑FSH, ↑LH (no surge), ↑GnRH
Ovaries continue to produce androgens under LH stimulation
What usually precedes menopause?
4-5 years of abnormal menstrual cycles
Source of estrogen after menopause?
Peripheral conversion of androgens
Best test to confirm menopause?
↑↑ FSH
What does Menopause produce?
“HHAVOC”
Hirsutism, Hot flashes, Atrophy of the Vagina, Osteoporosis, Coronary artery disease
Menopause before age 40 indicates…
Premature ovarian failure
Menorrhagia
Heavy and/or prolonged menses
Average length of menses
3-5 days
Average blood loss during menses
35mL (10-80)
Metrorrhagia
Irregular menses
Dysmenorrhea
Painful menses
As women approach menopause, how does their cycle change
Follicular part becomes shorter. Failure of ovaries to produce follicles and estrogen –> ↑↑ FSH and earlier LH/FSH surge
Perimenopause
What is it?
How long does it last?
Irregular/skipped menses and beginning of vasomotor symptoms
Can last 5-10 years before menopause
Menopause definition
12 months of amenorrhea
Mechanisms of osteoporosis in menopause
Estrogen –/ bone resorption by osteoclasts
Leuprolide
Mechanism
Uses
Toxicity
GnRH analog
Pulsatile –> Agonist
Continuous –> Antagonist (downregulation of GnRH receptors in pituitary –> ↓ FSH/LH
Pulsatile: treats infertility
Continuous: Endometriosis, Prostate cancer (w/ Flutamide), Uterine fibroids, Precocious puberty
Tox: Antiandrogen, Nausea, Vomiting
Testosterone, Methyltestosterone
Mechanism
Use
Toxicity
Agonist for androgen receptors
Treats: hypogonadism, Promotes development of secondary sex characteristics, Stimulation of anabolism to promote recovery after burn injury
Tox: Masculinization in females, Reduces intratresticular testosterone in males by inhibiting release of LH which leads to gonadal atrophy, Premature closure of epiphyseal plate, ↑LDL, ↓HDL
Names of antiandrogens
Finasteride, Flutamide, Ketoconazole, Spironolactone
Finasteride
Kind of drug
MoA
Uses
Tox
Antiandrogen
–/ 5α Reductase which turns T into DHT
Treats BPH and hair loss
Breast growth
Flutamide
Kind of drug
MoA
Uses
Antiandrogen
Nonsteroidal competitive inhibitor of androgens at the testosterone receptor
Treats prostate carcinoma
Ketoconazole
Kind of drug
MoA
Uses
Toxicity
Antiandrogen
Inhibits steroid synthesis (–/ 17,20 desmolase)
Treats PCOS to prevent hirsutism
Tox: gynecomastia and amenorrhea
Spironolactone
Kind of drug
MoA
Uses
Toxicity
Antiandrogen
Inhibits steroid binding
Treats PCOS to prevent hirsutism
Tox: gynecomastia and amenorrhea
Estrogens
Names
MoA
Use
Tox
Contraindication
Ethinly, Estradiol, DES, Mestranol
Binds Estrogen receptors
Treats Hypogonadism or Ovarian Failure, Menstrual abnormalities, HRT in postmenopausal women
Used in men to treat androgen dependent prostate cancer
Tox: ↑ risk of endometrial cancer, bleeding in postmenopausal women, clear cell carcinoma of the vagina/cervix in females exposed to DES in utero, ↑ risk of thrombi
ER+ breast cancer, history of DVTs
Names of Selective Estrogen Receptor Modulators (SERMs)
Clomiphene, Tamoxifen, Raloxifene
Clomiphene
Kind of Drug
MoA
Uses
Toxicity
SERM
Partial agonist at estrogen receptors in hypothalamus. Prevents normal feedback inhibition and ↑ LH and FSH from pituitary.
Treats infertility and PCOS
Tox: Hot flashes, ovarian enlargement, multiple simultaneous pregnancies, visual disturbances
Tamoxifen
Kind of Drug
MoA
Uses
SERM
Antagonist of estrogen receptors in breast tissue
Treats and prevents recurrence of ER+ breast cancer
Raloxifene
Kind of Drug
MoA
Uses
SERM
Agonist of estrogen receptors in bone and reduces bone resorption
Treats osteoporosis
Hormone Replacement Therapy
Uses
Toxicity
Used for the relief or prevention of menopausal symptoms (hot flashes, vaginal atrophy, etc) and osteoporosis (by ↑ estrogen –> ↓ osteoclast activity)
Unopposed use of estrogen –> ↑ risk of endometrial cancer, so progesterone is added. Possible ↑ CV risk
Anastrozole/Exemestane
MoA
Uses
Aromatase inhibitor used to treat postmenopausal women with breast cancer
Progestins
MoA
Uses
Binds progesterone receptors. Reduces growth and ↑ vascularization of endometrium
Used in oral contraceptives and treatment of endometrial cancer and abnormal uterine bleeding
Mifepristone (RU-486)
MoA
Co-administered with…
Use
Tox
Competitive inhibitor of progestins at progesterone receptor
Termination of pregnancy. Administered w/ misoprostol (PGE)
Tox: Heavy bleeding, GI effects (nausea, vomiting, anorexia), Abdominal pain
Oral Contraception
What does it consist of?
MoA
Contraindications
Progestins + Estrogen
E and P –/ LH/FSH which leads to prevention of estrogen surge. No estrogen surge –> no LH surge. No LH surge –> no ovulation
Progestins cause thickening of the cervical mucus, thereby limiting access of sperm to uterus.
Progestins –/ endometrial proliferation making it less suitable for implantation
Contraindicated in smokers >35 (CV events), Hx of Thromboembolism and stroke or Hx of estrogen dependent tumors
Terbutaline
MoA
Uses
β2 agonist that relaxes uterus
Reduces premature uterine contractions
Tamsulosin
MoA
Uses
Selectivity
α1 antagonist used to treat BPH by inhibiting smooth muscle contraction
Selective for α1A and α1D (on prostate) vs α1B (vasculature)
Sildenafil, Vardenafil
MoA
Uses
Tox
Contraindications
–/ Phosphodiesterase 5 causing an ↑ in cGMP, smooth muscle relaxation in corpus cavernosum, ↑ blood flow, and penile erection
Treats erectile dysfunction
Tox: “Hot and sweaty, but then Headache , Heartburn, Hypotension”
Headache, flushing, dyspnea, impaired blue-green color vision, Hypotension
Risk of life threatening hypotension in nitrate users
Danazol
MoA
Uses
Tox
Synthetic androgen that is a partial agonist at androgen receptor
Endometriosis and hereditary angioedema
Wt Gain, Edema, Acne, Hirsutism, Masculinization, ↓HDL, Hepatotoxicity
Endometriosis
What is it?
What tissue is affected?
What does it cause?
What causes it?
Non-neoplastic endometrial glands/stroma in abnormal locations In Ovary or on Peritoneum Cyclic bleeding (menstrual type) resulting in blood filled "chocolate cysts" Caused by retrograde menstrual flow
Endometriosis
Clinical manifestation?
Treatment
Dysmenorrhea, Menorrhagia, Dyspareunia, Infertility
Uterus is normal size
Treat with oral contraceptives, NSAIDs, Leuprolide, Danazol
Adenomyosis
What is it?
Clinical manifestation
Treatment
Endometrium within myometrium
Menorrhagia, Dysmenorrhea, Pelvic pain
Enlarged uterus
Hysterectomy
Cervical Dysplasia and Carcinoma In Situ
Description
Where does it begin and extend?
Classification
Histology
Disordered epithelial growth
Begins at basal layer of squamo-columnar junction and extends outwards
CIN1, CIN2, CIN3 (severe dysplasia or carcinoma in situ) depending on how high the basal cells extend
Koilocytes: raisinoid nuclei with perinuclear halo
Cervical Dysplasia and Carcinoma In Situ
Viral cause?
Mechanism of viral cause?
Prevention?
Risk if untreated
Risk factors
HPV16 and HPV18 (E6 –/ p53 andE7 –/ RB)
Vaccine available
May progress to invasive carcinoma if left untreated
Multiple sexual partners, smoking , early intercourse, HIV
Cervical Invasive Carcinoma
Most often what kind of carcinoma?
Screen?
Complications
Often squamous cell carcinoma
Pap smear
Lateral invasion can block ureter leading to renal failure
PCOS
PathoPhys
Gross
Clinical manifestation
Associated w/
Increased risk for
↑ frequency of pulsatile GnRA release –> ↑LH + ↓FSH –> anovulation –> no progesterone
Hyperandrogenism b/c of deranged steroid synthesis by Theca cells
Bilaterally enlarged, cystic ovaries
Amenorrhea, infertility, obesity, hirsutism
Associated with insulin resistance
Risk for endometrial cancer (↑ estrogen + no progesterone to oppose –> ↑ aromatization of testosterone in fat)
PCOS treatment
Wt reduction
Low does Oral Contraceptive or medroxyprogesterone (↓ LH and androgenesis)
Spironolactone (acne and hirsutism)
Clomiphene (infertility)
Meformin (diabetes or metabolic syndrome)
Endometrial hyperplasia
What is it?
What causes it?
Increased risk for…
Presentation
Risk factors
Abnormal endometrial gland proliferation
Caused by excess estrogen stimulation
↑ risk for endometrial carcinoma
Postmenopausal vaginal bleeding
Anovulatory cycle, HRT, PCOS, Granulosa Cell Tumor
Endometrial Carcinoma
Frequency
Epidemiology
Presentation
Typically preceded by
Risk factors
Prognosis
Most common gynecologic malignancy
Peak occurrence at 55-65
Vaginal bleeding
Typically preceded by endometrial hyperplasia
Prolonged use of estrogen w/o progesterone, obesity, diabetes, HTN, nulliparity, late menopause
↑ myometrial invasion –> poor prognosis
Types of Myometrial tumors
Leiomyoma (fibroid)
Leiomyosarcoma
Leiomyoma
Type of tumor
Frequency
Gross
Epidemiology
What kind of tissue
Malignant?
Myometrial tumor
Most common of all tumors in females
Multiple tumors with well-demarcated borders
↑ incidence in blacks. Peak at 20-40
Benign smooth muscle tumor
Malignant transformation to Leiomyosarcoma is rare
Leiomyoma
Hormone sensitive?
Presentation
Complications
Histology
Estrogen sensitive: tumor size ↑ w/ pregnancy and ↓ w/ menopause
May be asymptomatic, cause abnormal uterine bleeding, miscarriage
Severe bleeding may lead to Iron Deficiency Anemia
Whorled pattern of smooth muscle fibers
Leiomyosarcoma
Kind of tumor
Gross
Where does it arise from?
Epidemiology
Prognosis
Myometrial tumors
Bulky, irregular shaped tumor with areas of necrosis and hemorrhage. May protrude from cervix and bleed
Typically arising de novo
↑ incidence in middle aged black women
Highly aggressive w/ tendency to recur
Hydatidiform Moles
What are they?
Types
Presentation
Precursor of…
Serum marker
Gross
Potential complication
Treatment
Cystic swelling of chorionic villi and proliferation of chorionic epithelium (trophoblast)
Complete vs Partial
Presents with abnormal vaginal bleeding
Most common precursor of choriocarcinoma
↑βhCG
Honeycomb uterus or cluster of grapes appearance. Enlarged uterus
Uterine rupture
dilation and curettage and methotrexate
Complete Hydatidiform moles
Appearance
Fetus?
Karyotype
hCG
Uterine size
Conversion to choriocarcinoma
Fetal parts
Components
Risk of complications
Snowstorm appearance with no fetus during 1st sonogram
46XX, 46XY
↑↑↑↑ hCG
↑ uterine size
2% choriocarcinoma
No fetal parts
2 sperm (from same sperm that replicated) + empty egg
15-20% malignant trophoblastic disease
Partial Hydatidiform moles
Karyotype
hCG
Uterine size
Conversion to choriocarcinoma
Fetal parts
Components
Risk of complications
69XXX, 69XXY, 69XYY
↑ hCG
No change in uterine size
Rare choriocarcinoma
Has fetal parts
2 sperm + 1 egg
Low risk of malignancy
Classical Preeclampsia presentation
Pregnant women with HTN, Proteinuria, and Edema
Classical Presentation of Eclampsia
Preeclampsia + Seizures
Preeclampsia
Frequency
When
↑ risk in…
Caused by
Associated w/
Mortality results from
7% of pregnant women from 20 weeks to 6 weeks postpartum
↑ risk in pts w/ HTN, Diabetes, Chronic Renal Disease, Autoimmune disorders
Impaired vasodilation of spiral arteries –> Placental ischemia –> ↑ vascular tone
Associated with HELLP syndrome
Death from cerebral hemorrhage and ARDS
HELLP Syndrome
Hemolysis, Elevated Liver enzymes, Low Platelets
Clinical Manifestations of Preeclampsia
Lab findings
Headache, Blurred vision, Abdominal pain, Edema of face and extremities, altered mentation, hyperreflexia
Thrombocytopenia and Hyperuricemia
Treatment Preeclampsia
Delivery of fetus as soon as possible, Bed rest, monitoring, treat HTN
IV MgSulfate to prevent seizures